Despite great strides in development of effective vaccines, over two million deaths each year are due to vaccine-preventable diseases, indicating the need for increased accessibility to existing vaccines. In the proposed studies, we will explore a novel platform for mucosal immunization - sublingual immunization using mucoadhesive polymer films. Our hypothesis is that sublingual vaccine delivery will induce significant and protective immune responses and incorporation within mucoadhesive dissolvable polymer films containing mucosal adjuvants can enhance this response. Using inactivated influenza vaccine as a model antigen, we will perform in vivo immunization and challenge studies in a murine model to assess antibody and cellular immune responses, virus neutralization, and protective efficacy. We will determine the effectiveness of delivering influenza vaccine plus coadministered adjuvant in a single-dose mucoadhesive dissolvable film. We expect that the mucoadhesive film will result in a reduction in the amount of antigen needed to induce an immune response that is protective upon challenge. We will also better understand the role of mucosal adjuvants in modifying the immune response. These results will provide a foundation for further exploration of dissolvable films for co-administering adjuvants with inactivated influenza vaccines and other potential vaccine formulations for induction of broad mucosal protection. PUBLIC HEALTH RELEVANCE: In the proposed studies, we will explore a novel platform for mucosal immunization - sublingual immunization using mucoadhesive polymer films. Our hypothesis is that sublingual vaccine delivery will induce significant and protective immune responses and incorporation within mucoadhesive dissolvable polymer films containing mucosal adjuvants can enhance this response. These results will provide a foundation for further exploration of dissolvable films for co-administering adjuvants with influenza vaccines and other potential vaccine formulations for induction of broad mucosal protection.